Novel Device Therapies for Heart Failure.

Heart failure (HF) therapeutics have advanced significantly over the past few years [...].

Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy resulting from a mutation in one of several cardiac sarcomeric proteins [...].

The Roles of Coronary Computed Tomography Angiography in Characterizing Coronary Plaque: Screening, Treatment, and Prevention.

One of the major risk factors for coronary atherosclerosis is the gradual formation and maturation of coronary atherosclerotic plaque (CAP) [...].

Cardiac Amyloidosis: A Rare TTR Mutation Found in an Asian Female.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR) is a life-threatening, debilitating disease caused by abnormal formation and deposit of transthyretin (TTR) protein in multiple tissues, including myocardial extracellular matrix. It can be challenging to diagnose due to the myriad of presenting signs and symptoms. Additionally, numerous TTR mutations exist in certain ethnicities. Interestingly, our patient was discovered to have a very rare Gly67Ala TTR mutation typically not found in individuals of Asian descent. Recent advances in cardiovascular imaging techniques have allowed for earlier recognition and, therefore, management of this disease. Although incurable, there are now new, emerging treatments that are available for symptom control of cardiac amyloidosis, making early diagnosis vital for these patients, specifically their quality of life. CASE SUMMARY: We outline a case of a 50-year-old Asian female who was initially hospitalized for nausea and vomiting and persistent orthostatic hypotension. She underwent a multitude of laboratory and imaging tests, resulting in a diagnosis of cardiac amyloidosis, which was confirmed to be due to a rare TTR mutation via genetic testing. CONCLUSIONS: Our objective is to describe various TTR mutations, existing diagnostic imaging modalities, and available treatments, as well as highlight the importance of early screening and awareness of cardiac amyloidosis, allowing for quicker diagnosis and treatment of this disease.

2022 HRS expert consensus statement on evaluation and management of arrhythmic risk in neuromuscular disorders.

This international multidisciplinary document is intended to guide electrophysiologists, cardiologists, other clinicians, and health care professionals in caring for patients with arrhythmic complications of neuromuscular disorders (NMDs). The document presents an overview of arrhythmias in NMDs followed by detailed sections on specific disorders: Duchenne muscular dystrophy, Becker muscular dystrophy, and limb-girdle muscular dystrophy type 2; myotonic dystrophy type 1 and type 2; Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B; facioscapulohumeral muscular dystrophy; and mitochondrial myopathies, including Friedreich ataxia and Kearns-Sayre syndrome, with an emphasis on managing arrhythmic cardiac manifestations. End-of-life management of arrhythmias in patients with NMDs is also covered. The document sections were drafted by the writing committee members according to their area of expertise. The recommendations represent the consensus opinion of the expert writing group, graded by class of recommendation and level of evidence utilizing defined criteria. The recommendations were made available for public comment; the document underwent review by the Heart Rhythm Society Scientific and Clinical Documents Committee and external review and endorsement by the partner and collaborating societies. Changes were incorporated based on these reviews. By using a breadth of accumulated available evidence, the document is designed to provide practical and actionable clinical information and recommendations for the diagnosis and management of arrhythmias and thus improve the care of patients with NMDs.

Meta-Analysis Comparing WatchmanTM and Amplatzer Devices for Stroke Prevention in Atrial Fibrillation.

Background: For patients with atrial fibrillation who are at high risk for bleeding or who cannot tolerate oral anticoagulation, left atrial appendage (LAA) closure represents an alternative therapy for reducing risk for thromboembolic events. Objectives: To compare the efficacy and safety of the Amplatzer and WatchmanTM LAA closure devices. Methods: A meta-analysis was performed of studies comparing the safety and efficacy outcomes of the two devices. The Newcastle-Ottawa Scale was used to appraise study quality. Results: Six studies encompassing 614 patients were included in the meta-analysis. Overall event rates were low for both devices. No significant differences between the devices were found in safety outcomes (i.e., pericardial effusion, cardiac tamponade, device embolization, air embolism, and vascular complications) or in the rates of all-cause mortality, cardiac death, stroke/transient ischemic attack, or device-related thrombosis. The total bleeding rate was significantly lower in the WatchmanTM group (Log OR = -0.90; 95% CI = -1.76 to -0.04; p = 0.04), yet no significant differences was found when the bleeding rate was categorized into major and minor bleeding. Total peridevice leakage rate and insignificant peridevice leakage rate were significantly higher in the WatchmanTM group (Log OR = 1.32; 95% CI = 0.76 to 1.87; p < 0.01 and Log OR = 1.11; 95% CI = 0.50 to 1.72; p < 0.01, respectively). However, significant peridevice leakages were similar in both the devices. Conclusions: The LAA closure devices had low complication rates and low event rates. Efficacy and safety were similar between the systems, except for a higher percentage of insignificant peridevice leakages in the WatchmanTM group. A randomized controlled trial comparing both devices is underway, which may provide more insight on the safety and efficacy outcomes comparison of the devices.

Association of Race With Disease Expression and Clinical Outcomes Among Patients With Hypertrophic Cardiomyopathy.

Importance: Racial differences are recognized in multiple cardiovascular parameters, including left ventricular hypertrophy and heart failure, which are 2 major manifestations of hypertrophic cardiomyopathy. The association of race with disease expression and outcomes among patients with hypertrophic cardiomyopathy is not well characterized. Objective: To assess the association between race, disease expression, care provision, and clinical outcomes among patients with hypertrophic cardiomyopathy. Design, Setting, and Participants: This retrospective cohort study included data on black and white patients with hypertrophic cardiomyopathy from the US-based sites of the Sarcomeric Human Cardiomyopathy Registry from 1989 through 2018. Exposures: Self-identified race. Main Outcomes and Measures: Baseline characteristics; genetic architecture; adverse outcomes, including cardiac arrest, cardiac transplantation or left ventricular assist device implantation, implantable cardioverter-defibrillator therapy, all-cause mortality, atrial fibrillation, stroke, and New York Heart Association (NYHA) functional class III or IV heart failure; and septal reduction therapies. The overall composite outcome consists of the first occurrence of any component of the ventricular arrhythmic composite end point, cardiac transplantation, left ventricular assist device implantation, NYHA class III or IV heart failure, atrial fibrillation, stroke, or all-cause mortality. Results: Of 2467 patients with hypertrophic cardiomyopathy at the time of analysis, 205 (8.3%) were black (130 male [63.4%]; mean [SD] age, 40.0 [18.6] years) and 2262 (91.7%) were white (1351 male [59.7%]; mean [SD] age, 45.5 [20.5] years). Compared with white patients, black patients were younger at the time of diagnosis (mean [SD], 36.5 [18.2] vs 41.9 [20.2] years; P < .001), had higher prevalence of NYHA class III or IV heart failure at presentation (36 of 205 [22.6%] vs 174 of 2262 [15.8%]; P = .001), had lower rates of genetic testing (111 [54.1%] vs 1404 [62.1%]; P = .03), and were less likely to have sarcomeric mutations identified by genetic testing (29 [26.1%] vs 569 [40.5%]; P = .006). Implantation of implantable cardioverter-defibrillators did not vary by race; however, invasive septal reduction was less common among black patients (30 [14.6%] vs 521 [23.0%]; P = .007). Black patients had less incident atrial fibrillation (35 [17.1%] vs 608 [26.9%]; P < .001). Black race was associated with increased development of NYHA class III or IV heart failure (hazard ratio, 1.45; 95% CI, 1.08-1.94) which persisted on multivariable Cox proportional hazards regression (hazard ratio, 1.97; 95% CI, 1.34-2.88). There were no differences in the associations of race with stroke, ventricular arrhythmias, all-cause mortality, or the overall composite outcome. Conclusions and Relevance: The findings suggest that black patients with hypertrophic cardiomyopathy are diagnosed at a younger age, are less likely to carry a sarcomere mutation, have a higher burden of functionally limited heart failure, and experience inequities in care with lower use of invasive septal reduction therapy and genetic testing compared with white patients. Further study is needed to assess whether higher rates of heart failure may be associated with underlying ancestry-based disease pathways, clinical management, or structural inequities.

Baseline Characteristics of the VANISH Cohort.

BACKGROUND: The VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) targeted young sarcomeric gene mutation carriers with early-stage hypertrophic cardiomyopathy (HCM) to test whether valsartan can modify disease progression. We describe the baseline characteristics of the VANISH cohort and compare to previous trials evaluating angiotensin receptor blockers. METHODS: Applying a randomized, double-blinded, placebo-controlled design, 178 participants with nonobstructive HCM (age, 23.3±10.1 years; 61% men) were randomized in the primary cohort and 34 (age, 16.5±4.9 years; 50% men) in the exploratory cohort of sarcomeric mutation carriers without left ventricular hypertrophy. RESULTS: In the primary cohort, maximal left ventricular wall thickness was 17±4 mm for adults and Z score 7.0±4.5 for children. Nineteen percent had late gadolinium enhancement on cardiac magnetic resonance. Mean peak oxygen consumption was 33 mL/kg per minute, and 92% of participants were New York Heart Association functional class I. New York Heart Association class II was associated with older age, MYH7 variants, and more prominent imaging abnormalities. Six previous trials of angiotensin receptor blockers in HCM enrolled a median of 24 patients (range, 19-133) with mean age of 51.2 years; 42% of patients were in New York Heart Association class ≥II, and sarcomeric mutations were not required. CONCLUSIONS: The VANISH cohort is much larger, younger, less heterogeneous, and has less advanced disease than prior angiotensin receptor blocker trials in HCM. Participants had relatively normal functional capacity and mild HCM features. New York Heart Association functional class II symptoms were associated with older age, more prominent imaging abnormalities, and MYH7 variants, suggesting both phenotype and genotype contribute to disease manifestations. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01912534.

Prevalence and Progression of Late Gadolinium Enhancement in Children and Adolescents With Hypertrophic Cardiomyopathy.

BACKGROUND: Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is believed to represent dense replacement fibrosis. It is seen in ≈60% of adult patients with hypertrophic cardiomyopathy (HCM). However, the prevalence of LGE in children and adolescents with HCM is not well established. In addition, longitudinal studies describing the development and evolution of LGE in pediatric HCM are lacking. This study assesses the prevalence, progression, and clinical correlations of LGE in children and adolescents with, or genetically predisposed to, HCM. METHODS: CMR scans from 195 patients ≤21 years of age were analyzed in an observational, retrospective study, including 155 patients with overt HCM and 40 sarcomere mutation carriers without left ventricular (LV) hypertrophy. The extent of LGE was quantified by measuring regions with signal intensity >6 SD above nulled remote myocardium. RESULTS: Patients were 14.3±4.5 years of age at baseline and 68% were male. LGE was present in 70 (46%) patients with overt HCM (median extent, 3.3%; interquartile range, 0.8-7.1%), but absent in mutation carriers without LV hypertrophy. Thirty-one patients had >1 CMR (median interval between studies, 2.4 years; interquartile range, 1.5-3.2 years). LGE was detected in 13 patients (42%) at baseline and in 16 patients (52%) at follow-up CMR. The median extent of LGE increased by 2.4 g/y (range, 0-13.2 g/y) from 2.9% (interquartile range, 0.8-3.2%) of LV mass to 4.3% (interquartile range, 2.9-6.8%) ( P=0.02). In addition to LGE, LV mass and left atrial volume, indexed to body surface area, and z score for LV mass, as well, increased significantly from first to most recent CMR. CONCLUSIONS: LGE was present in 46% of children and adolescents with overt HCM, in contrast to ≈60% typically reported in adult HCM. In the subset of patients with serial imaging, statistically significant increases in LGE, LV mass, and left atrial size were detected over 2.5 years, indicating disease progression over time. Further prospective studies are required to confirm these findings and to better understand the clinical implications of LGE in pediatric HCM.

A Novel Mechanism for Improved Exercise Performance in Pediatric Fontan Patients After Cardiac Rehabilitation.

Patients with a Fontan circulation have impaired exercise capacity. Cardiac rehabilitation (CR) has shown promise in enhancing peak exercise parameters in this population, but an improvement in submaximal exercise has not been consistently demonstrated. We assessed the hypothesis that participation in CR will be associated with more efficient oxygen extraction and ventilation during submaximal exercise. In this prospective study, pediatric Fontans completed two 60 min CR sessions per week for 12 weeks. Cardiopulmonary exercise testing and stress echocardiography were performed at baseline and last CR session, and then compared with a paired sample t test. Ten pediatric Fontans completed the study. Five had tricuspid atresia and five had hypoplastic left heart syndrome. No serious adverse events occurred during CR sessions. Peak indexed oxygen consumption increased by a mean of 3.7 mL/kg/min (95% CI 1.5-5.9; p = 0.004), and peak oxygen pulse increased by a mean of 0.9 mL/beat (95% CI 0.4-1.4; p = 0.004). The peak respiratory exchange ratio did not change significantly. The significant difference in oxygen pulse became evident during submaximal exercise without a corresponding difference in echocardiographic stroke volume. Indexed oxygen consumption at ventilatory anaerobic threshold increased by a mean of 3.0 mL/kg/min (95% CI - 0.07 to 6.0; p = 0.055). The slope for the volume of expired ventilation to volume of carbon dioxide production improved by a mean of 4.5 (95% CI - 8.4 to - 0.6; p = 0.03). We observed significant improvements in both submaximal and peak exercise performance in pediatric Fontans undergoing CR with no serious adverse events. These changes appeared to be mediated, at least in part, by more efficient oxygen extraction and ventilation.

Hypertrophic Cardiomyopathy Genotype Prediction Models in a Pediatric Population.

The Toronto Hypertrophic Cardiomyopathy (HCM) Genotype Score and Mayo HCM Genotype Predictor are risk assessment models developed to estimate a patient's likelihood of testing positive for a pathogenic variant causative of HCM. These models were developed from adult populations with HCM based on factors that have been associated with a positive genotype and have not been validated in external populations. The purpose of this study was to evaluate the overall predictive abilities of these models in a clinical pediatric HCM setting. A retrospective medical record review of 77 pediatric patients with gene panel testing for HCM between September 2005 and June 2015 was performed. Clinical and echocardiographic variables used in the developed models were collected and used to calculate scores for each patient. To evaluate model performance, the ability to discriminate between a carrier and non-carrier was assessed by area under the ROC curve (AUC) and overall calibration was evaluated by the Hosmer-Lemeshow goodness-of-fit statistic. Discrimination assessed by AUC was 0.72 (P < 0.001) for the Toronto model and 0.67 (P = 0.004) for the Mayo model. The Toronto model and the Mayo model showed P values of 0.36 and 0.82, respectively, for model calibration. Our findings suggest that these models are useful in predicting a positive genetic test result in a pediatric HCM setting. They may be used to aid healthcare providers in communicating risk and enhance patient decision-making regarding pursuit of genetic testing.

Biomarkers of cardiovascular stress and fibrosis in preclinical hypertrophic cardiomyopathy.

Objective: Sarcomeric gene mutation carriers without overt left ventricular hypertrophy (G+/LVH-) can harbour subclinical changes in cardiovascular structure and function that precede the development of hypertrophic cardiomyopathy (HCM). We sought to investigate if circulating biomarkers of cardiovascular stress and collagen metabolism among G+/LVH- individuals, measured at rest and following exercise provocation, yield further insights into the underlying biology of HCM. Methods: We studied 76 individuals with overt HCM, 50 G+/LVH- individuals and 41 genotype-negative related controls enrolled in a cross-sectional, multicentre observational study (HCMNet). Biomarkers of cardiac stress (N-terminal pro-B-type natriuretic peptide, NT-proBNP; high-sensitivity troponin I, hsTnI; soluble ST2) and fibrosis (carboxy-terminal propeptide of procollagen type I; C-terminal telopeptide of type I collagen; galectin-3; periostin) were measured. Results: Individuals with overt HCM had elevated NT-proBNP and hsTnI compared with G+/LVH- subjects and controls at rest, along with an exaggerated increase in NT-proBNP and hsTnI in response to exercise. We found no detectable differences in resting or exercise-provoked biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with healthy controls despite subtle echocardiographic differences in cardiac structure and function. Conclusion: Dynamic exercise testing exaggerated resting differences in natriuretic peptides and troponin elevations among individuals with overt HCM. In contrast, we found no differences in biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with controls even after maximal exercise provocation. Our findings highlight the need for continued investigation into early phenotypes of sarcomeric gene mutations and the evolution of HCM.

Case report: Left ventricular noncompaction cardiomyopathy and RASopathies.

The following is a case report of 6 patients with Noonan syndrome (NS) and/or a related RASsopathy that also have evidence of left ventricular noncompaction cardiomyopathy (LVNC). Noonan syndrome,a type of RASopathy, is an autosomal dominant disorder that is typically associated with congenital heart defects and hypertrophic cardiomyopathy. There have been minimal reports of Noonan syndrome or other RASopathy and the association of LVNC. This report promulgates 6 nonrelated cases of Noonan syndrome or unspecified RASopathy and LVNC.

Cardiomyopathies Due to Left Ventricular Noncompaction, Mitochondrial and Storage Diseases, and Inborn Errors of Metabolism.

The normal function of the human myocardium requires the proper generation and utilization of energy and relies on a series of complex metabolic processes to achieve this normal function. When metabolic processes fail to work properly or effectively, heart muscle dysfunction can occur with or without accompanying functional abnormalities of other organ systems, particularly skeletal muscle. These metabolic derangements can result in structural, functional, and infiltrative deficiencies of the heart muscle. Mitochondrial and enzyme defects predominate as disease-related etiologies. In this review, left ventricular noncompaction cardiomyopathy, which is often caused by mutations in sarcomere and cytoskeletal proteins and is also associated with metabolic abnormalities, is discussed. In addition, cardiomyopathies resulting from mitochondrial dysfunction, metabolic abnormalities, storage diseases, and inborn errors of metabolism are described.

Early detection of acute kidney injury after pediatric cardiac surgery.

Acute kidney injury (AKI) is increasingly recognized as a common problem in children undergoing cardiac surgery, with well documented increases in morbidity and mortality in both the short and the long term. Traditional approaches to the identification of AKI such as changes in serum creatinine have revealed a large incidence in this population with significant negative impact on clinical outcomes. However, the traditional diagnostic approaches to AKI diagnosis have inherent limitations that may lead to under-diagnosis of this pathologic process. There is a dearth of randomized controlled trials for the prevention and treatment of AKI associated with cardiac surgery, at least in part due to the paucity of early predictive biomarkers. Novel non-invasive biomarkers have ushered in a new era that allows for earlier detection of AKI. With these new diagnostic tools, a more consistent approach can be employed across centers that may facilitate a more accurate representation of the actual prevalence of AKI and more importantly, clinical investigation that may minimize the occurrence of AKI following pediatric cardiac surgery. A thoughtful management approach is necessary to mitigate the effects of AKI after cardiac surgery, which is best accomplished in close collaboration with pediatric nephrologists. Long-term surveillance for improvement in kidney function and potential development of chronic kidney disease should also be a part of the comprehensive management strategy.

PROGRESSION OF CHRONIC KIDNEY DISEASE AFTER ACUTE KIDNEY INJURY.

The incidence of chronic kidney disease (CKD) in children and adults is increasing. Cardiologists have become indispensable members of the care provider team for children with CKD. This is partly due to the high incidence of CKD in children and adults with congenital heart disease, with current estimates of 30-50%. In addition, the high incidence of acute kidney injury (AKI) due to cardiac dysfunction or following pediatric cardiac surgery that may progress to CKD is also well documented. It is now apparent that AKI and CKD are uniquely intertwined as interconnected syndromes. Furthermore, the well-known long-term cardiovascular morbidity and mortality associated with CKD require the joint attention of both nephrologists and cardiologists. Children with both congenital heart disease and CKD are increasingly surviving to adulthood, with synergistically negative medical, financial, and quality of life impact. An improved understanding of the epidemiology, mechanisms, early diagnosis, and preventive measures is of importance to cardiologists, nephrologists, scientists, economists, and policy makers alike. Herein, we report the current definitions, epidemiology, and complications of CKD in children, with an emphasis on children with congenital heart disease. We then focus on the clinical and experimental evidence for the progression of CKD after episodes of AKI commonly encountered in children with heart disease, and explore the role of novel biomarkers for the prediction of CKD progression.